Regulatory Toxicology and Pharmacology 61 (2011) S51–S59

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Regulatory Toxicology and Pharmacology

journal homepage: www.elsevier.com/locate/yrtph

Regular Article

Estimation of nicotine and tar yields from human-smoked cigarettes before and
after the implementation of the cigarette ignition propensity regulations in Canada
France Côté a,*, Cécile Létourneau a,1, Gavin Mullard b,2, Richard Voisine a
a
Imperial Tobacco Canada Ltd., 3711 St-Antoine Street West, Montreal, Quebec, Canada H4C 3P6
b
British American Tobacco, Group Research and Development, Southampton SO15 8TL, UK

a r t i c l e i n f o a b s t r a c t

Article history: In 2005, Human-Smoked (HS) tar and nicotine yields from commercial Canadian cigarettes were deter-
Received 5 January 2010 mined using a part filter analysis method to obtain estimates representative of human smoking behavior.
Available online 18 March 2010 In 2006, new cigarette designs were introduced to ensure compliance with the Canadian Low Ignition
Propensity (LIP) regulations. It was not known how the changes in product design would affect HS yields.
Keywords: To assess the impact of the cigarette design modifications on HS yields, a further group of Canadian smok-
Cigarette ers was recruited for smoking the modified version of 10 products previously assessed. No differences in
Smoke
estimated HS tar yields were found between products following product modification. The HS nicotine
Nicotine
Tar
yield was different for one product. In general, HS yields were higher than ISO machine yields while Cana-
Human-smoked yield dian intense machine yields were more representative of the maximum HS yields. The same product
Low ignition propensity ranking order was obtained for HS yields and the two machine yields but differences between the mean
HS yields and ISO yields were smaller as the product ISO yields increased. Higher HS yields were mea-
sured when products were smoked by male smokers. The methodology used in this study showed the
wide range of HS yields obtained by smokers as well as a good degree of stability in average HS yields
just before and after the introduction of LIP regulations.
Ó 2010 Elsevier Inc. Open access under CC BY-NC-ND license.

1. Introduction
Cigarette yields obtained by using the U.S. Federal Trade Com-
mission (FTC) and the International Organization for Standardiza-
tion (ISO) machine-smoking regimes (35 mL puffs, 2 s duration
once a minute) do not represent the amounts of nicotine and tar
(nicotine free dry particulate matter) obtained by most smokers
(Hammond et al., 2007). Several studies have shown that the ISO
yields underestimate human yields (Gori and Lynch, 1985;
Hammond et al., 2006). In recent years, more intense alternative
smoking regimes have been introduced in addition to the ISO/
FTC cigarette yields. The Commonwealth of Massachusetts requires
the testing of cigarettes with 45 mL puffs of 2 s duration taken
twice per minute, and with 50% filter vent holes blocked
(Commonwealth of Massachusetts, 2004). In Canada, both ISO
and an intense smoking regime (55 mL puffs, 2 s duration twice
per minute, 100% filter vent holes blocked) are used as testing stan-
dards (Health Canada, 2000). Mainstream smoke constituent yields
typically increase in the ISO < Massachusetts < Canadian intense
* Corresponding author. Fax: +1 514 932 7033.
E-mail address: fcote@itl.ca (F. Côté).
1
Retired from Imperial Tobacco Canada Ltd.
2
Present address: British American Tobacco, 4 Temple Place, London WC2R 2PG,
UK.
smoking regimes (Counts et al., 2006). The Canadian intense smok-
ing regime is considered to produce maximum yields (Hammond
et al., 2007).
The great range of human puffing behavior is one of the main
factors contributing to the variation in cigarette smoke exposure
between smokers smoking the same cigarette product (Zacny
and Stitzer, 1996; Hammond et al., 2005). Therefore, machine-
smoking under defined conditions cannot duplicate the variety of
human puffing profiles. One way of estimating human exposure
to specific cigarette smoke constituents is to measure relevant bio-
markers in body fluids. Less invasive and expensive methods can
also be used to estimate human exposure to cigarette smoke: the
duplication of human puffing topography and the filter analysis
methodology. The latter is used to estimate Human-Smoked (HS)
cigarette yields or Mouth Level Exposure (MLE) by comparison of
the nicotine content and UV absorbance of cigarette filter extracts
from human-smoked cigarettes with those from machine-smoked
cigarettes for which smoke yield is known. This is possible since
the yields of nicotine or tar in the smoke and the amounts retained
in the filter are related to the filtration efficiency of the filter. The
HS yield estimates represent the maximum amount of smoke con-
stituents that exit the filter and therefore, the maximum amount of
smoke the smoker could inhale. No account is taken for smoke
spilled by the smoker prior to inhalation, or smoke exhaled. The fil-
ter analysis method is also less complex than human puffing

0273-2300 Ó 2010 Elsevier Inc. Open access under CC BY-NC-ND license.

doi:10.1016/j.yrtph.2010.03.004
S52 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59

topography duplication and does not interfere with the smoking
process. It only involves the collection of spent filters from smokers
smoking in their everyday environment. A study conducted by
Shepperd et al. (2006) compared the analysis of the whole filter
with the analysis of a 10 mm section from the mouth-end of filters.
The part filter analysis methodology was shown to give more accu-
rate estimates of HS tar and nicotine yields because it is less sus-
ceptible to the influence of different puff flow rates on filtration
efficiency. The part filter analysis has also been shown to correlate
well with salivary cotinine and urinary excretion of nicotine
metabolites (St. Charles et al., 2006; Shepperd et al., 2009; Morin
et al., this issue). A review of several cigarette filter-based assays
recently published highlighted a number of gaps in the part filter
analysis methodology knowledge (Pauly et al., 2009). New infor-
mation addressing these issues were discussed by St. Charles
et al. (2009).
Since October 2005, all cigarettes manufactured or imported for
sale in Canada are required to meet the LIP Regulations standard:
cigarettes must burn to their full length no more than 25% of the
time when tested on 10 layers of filter paper using ASTM Interna-
tional method E2187-04, dated July 1, 2004 and entitled Standard
Test Method for Measuring the Ignition Strength of Cigarettes
(Health Canada, 2005). To comply with these regulations while
maintaining ISO tar and nicotine yields of the brands, several
changes to the cigarette product designs had to be made. The ma-
jor modification was the use of banded cigarette paper in the Cana-
dian products. The banded paper is designed to have intermittent
lower permeability bands to reduce cigarette burn rate. The ciga-
rette should self extinguish when the lit end comes into contact
with a band while smouldering. The impact of the changes in cig-
arette design due to the new LIP regulations on HS yields is not
known. Smokers might need to light the cigarette more than once
if the cigarette extinguishes between puffs. Also, they can modify
their smoking behavior when they perceive that the cigarette
starts to self extinguish. These changes in smoking behavior could
affect the HS yields.
Hammond et al. (2006) recently reported estimates of cigarette
nicotine and tar yields of products smoked by Canadian smokers
obtained by duplicating human smoking topography. The products
used in their study were manufactured before the implementation
of the LIP regulations. To our knowledge, Canadian HS cigarette
yields (mg/cig), estimated using the part filter analysis methodol-
ogy, have not been reported, except in this study and the related
paper in this issue (Mariner et al., this issue).
The main objective of this study was to use the part filter anal-
ysis method to obtain estimates of HS nicotine and tar yields from
Canadian smokers smoking their own cigarette brands in their
everyday environment and compare the HS yields from cigarettes
produced before and after the introduction of the LIP regulations.
The influence of the cigarette product format and smoker demo-
graphics has been examined and the estimated HS yields were
compared with the two Canadian regulatory smoking regime
yields. Illicit products, which in 2006 comprised 16.5% of the mar-
ket (32.7% in 2008), are not compliant with the Canadian legisla-
tion and were excluded from the study (Imperial Tobacco
Canada, 2008).
2. Materials and methods
2.1. Study design
HS nicotine and tar yields were estimated for 12 flue-cured Vir-
ginia commercial cigarette products during a study conducted
from April to May 2005. The study was repeated from April to
May 2006 using 10 out of the 12 products previously assessed.
Only data from the 10 products tested in both years have been re-
ported in this paper. Subjects were recruited in the field by an
external agency in three major Canadian cities (Montreal, Toronto
and Vancouver). The selected products covered the range of yields
and the two main formats available in the Canadian market
(Tables 1 and 2). Cigarettes of King Size (KS) format had a total
length of 84 mm and a 20 mm filter. The Regular Size (RS) cigarettes
were 72 mm long with 17 mm filters. The major difference between
2005 and 2006 products was that the 2006 products were made
with LIP cigarette paper. For some products, the tobacco density, fil-
ter ventilation and pressure drops were also slightly modified. For
all products, tar and nicotine mainstream ISO and Canadian intense
yields were determined using the standard smoking protocols
(Health Canada, 1999). The ISO yields shown in Table 1 were mea-
sured on the same samples that were used for the market surveys.
For each year and each product, the Canadian intense yields re-
ported in Table 2 are the average yields measured from 9 to 10 sam-
ples obtained from different months during the year.
For each study year, the recruitment target was between 50 and
60 smokers per product with gender and age group quotas to rep-
resent as much as possible the demographic profiles of consumers
of the products being assessed. The recruited adult smokers with a
minimum age of 19 years old were regular users of the target prod-
uct for at least six months and smoking a minimum of five ciga-
rettes per day. The subjects who participated in the 2005 study
were not recruited for the 2006 study. All participants were re-
minded of the risks of smoking before agreeing to participate and
those planning to quit smoking were excluded. All subjects gave
written informed consent and were paid $60 for completing each
study.

Table 1
Cigarette products list and machine-smoked ISO nicotine and tar yields.

Format Product ISO nicotine yield (mg/cig)c mean (SD) ISO tar yield (mg/cig)c mean (SD)
2005 2006 2005 2006
King sizea A 0.11 (0.01) 0.16 (0.01) 0.9 (0.3) 1.2 (0.2)
B 0.40 (0.07) 0.37 (0.04) 3.9 (0.9) 3.9 (0.3)
C 0.61 (0.03) 0.67 (0.06) 5.4 (0.4) 6.3 (0.6)
D 1.06 (0.04) 1.06 (0.08) 10.0 (1.0) 10.5 (0.9)
E 1.30 (0.07) 1.19 (0.01) 14.7 (1.4) 13.8 (0.3)
Regular sizeb F 0.34 (0.03) 0.38 (0.04) 3.3 (0.4) 3.6 (0.3)
G 0.60 (0.03) 0.52 (0.02) 5.3 (0.6) 4.6 (0.3)
H 0.81 (0.02) 0.75 (0.04) 7.6 (0.5) 6.9 (0.6)
I 1.02 (0.07) 1.12 (0.04) 11.5 (0.5) 12.6 (0.5)
J 1.25 (0.03) 1.25 (0.02) 14.4 (0.9) 14.0 (0.5)
a
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.
c
Tar and nicotine yields measured according to ISO 3308:2000.
 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59 S53

Table 2
Cigarette products list and machine-smoked intense nicotine and tar yields.

Format Product Intense nicotine yield (mg/cig)c mean (SD) Intense tar yield (mg/cig)c mean (SD)
2005 2006 2005 2006
King sizea A 1.49 (0.09) 1.56 (0.06) 18.9 (1.4) 21.3 (1.4)
B 1.81 (0.06) 1.80 (0.07) 24.4 (0.7) 25.1 (0.6)
C 2.41 (0.07) 2.36 (0.06) 29.1 (1.1) 29.1 (1.2)
D 2.66 (0.12) 2.53 (0.06) 32.5 (1.0) 31.5 (0.7)
E 2.65 (0.13) 2.52 (0.05) 33.6 (1.4) 33.0 (0.5)
Regular sizeb F 1.86 (0.07) 1.89 (0.06) 26.0 (1.3) 26.7 (0.4)
G 2.12 (0.13) 2.04 (0.04) 26.9 (1.1) 25.8 (0.8)
H 2.16 (0.13) 2.11 (0.08) 27.2 (1.1) 26.3 (0.8)
I 2.26 (0.07) 2.31 (0.05) 29.6 (1.2) 30.9 (0.5)
J 2.60 (0.07) 2.69 (0.05) 33.8 (1.1) 33.8 (0.6)
a
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.
c
Smoking conditions: 55 mL puff volume, 2 s duration, 30 s interval, 100% ventilation holes blocked (Health Canada, 2000). Average of 9–10 samples collected from
different months during the study year.

To estimate the HS yields, 10 mm mouth-end portions of freshly
smoked filter tips were collected using a specially designed filter
cutter/collector. Each cutter/collector also had an anti-tamper seal
attached to the storage box to prevent/avoid subject/sample inter-
ference. Subjects were instructed how to use the filter cutter/col-
lector when they visited the agency. They were permitted to
smoke ad libitum during the studies. The objective was to collect
a minimum of 15 filter tip portions. Subjects were given one or
two cigarette packs of their own products (depending upon their
self-reported daily consumption) and they had to return the cut-
ter/collector once they had collected enough tips. Following receipt
by the laboratory, the cutter/collector was opened and 15 tips were
selected. Poorly cut filter tips, otherwise damaged or heavily
stained with lipstick were considered less acceptable and were
analyzed only where there was a major shortfall in sample return
from a given subject. Eighty-seven of the total 1086 subjects re-
tained during the two study years, returned their cutter/collectors
containing less than 15 filter tip portions (number of cutters with
14 filter tips: 53, 13 filter tips: 28, 12 filter tips: 4, 11 filter tips: 1,
10 filter tips: 1). Data from all those subjects was included in the
analysis.
2.2. Filter tip analysis
HS nicotine and tar yields were estimated using previously de-
scribed methodology (Shepperd et al., 2006; St. Charles et al., 2006)
with some modifications described below. For each of the 10 prod-
ucts, a calibration curve was constructed by smoking the cigarettes
using a rotary smoking machine (RM20, Borgwaldt, Germany) at
specific regimes (Table 3). All calibration smoking regimes used
44 mm Cambridge Filter Pads (CFP) except regime 8 which re-
quired a 92 mm CFP for products with ISO tar yields higher than
4 mg. This was necessary to avoid overloading the pad with tar
(and risking losses) and consequently underestimating the amount
of tar generated. Regime 10 was performed for RS products only.
These regimes were selected in order to cover the anticipated HS
yields. Un-smoked filters were used as blanks (regime 0).
For each smoking regime, five cigarettes were smoked onto a 44
or 92 mm pre-weighed CFP to trap >99% of the total particulate
matter present in the mainstream smoke. A 10 mm portion was
then accurately cut from the mouth-end of each of the five ciga-
rette filters using a filter collector. The cut filter tips were analyzed
for tar and nicotine content as described below.
The 44 mm CFP was reweighed, to obtain total particulate
matter yield, and then extracted in 20 mL of propan-2-ol contain-
ing n-heptadecane (internal standard for nicotine, 0.25 mg/mL)
and ethanol (internal standard for water, 4.0 mg/mL). The extrac-
tion of the 92 mm CFP was performed into 40 mL of solvent with
appropriate correction for dilution. The extract was tested for nic-
otine content by Gas Chromatography (GC)/Flame Ionization
Detection (Agilent 6890 GC System), using a 25 m  0.53 mm 
2.0 lm CP Wax 52 CB fused silica column, and for water by GC-
Thermal Conductivity Detection (Agilent 6890 GC System), using
a 10 m  0.53 mm id. fused silica column containing Poraplot Q.
Cigarette filter tips collected from calibration and each subject
were analyzed for nicotine content (mg/tip) and UV absorbance

Table 3
Smoking regimes used to construct calibration curves for each cigarette product.

Regime Puff volume (mL) Puff duration (s) Interval between puffs (s) Butt length or puff number 1–3 mg/cig ISO tar products >4 mg/cig ISO tar products
0 Blank X X
1 40 2 60 4 Puffs X X
2 40 2 30 OTc + 3 mm X X
3 50 1.5 60 4 Puffs X
4 50 1.5 60 OT + 3 mm X
5 50 1.5 30 OT + 3 mm X X
6 70 1.5 60 4 Puffs X
7 70 1.5 30 OT + 3 mm X
8a 70 1.5 20 OT + 3 mm X
9 70 1.5 20 OT + 3 mm X
10b 40 2 30 OT + 10 mm X X

Regime 0 provides un-smoked blank tips.

a
Use 92 mm Cambridge filter pad for regime 8.
b
For calibration of regular length products only.
c
OT: over-tipping (tipping is an impermeable paper wrapper that holds filter and tobacco rod together).
S54 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59

(310 nm) (UVabs/tip). The 15 tips from the subjects were separated 35
at random into three batches of five and the length of each tip was
accurately measured. Each batch was extracted in 20 mL methanol
containing 0.05 mg/mL n-heptadecane as internal standard and 30
analyzed for nicotine using the GC-FID and column described

Estimated HS tar yield (mg/cig)

above. The tar content of the extract was estimated with an UV
25
absorbance method using a modified HPLC system (HP1100, Hew-
lett Packard) comprising a mobile phase, a pump, an autosampler
with injection facility and an UV detector set to determine absor- 20
bance at 310 nm. The column was replaced with a length of PeekÒ
tubing providing a dead-space of suitable volume to separate injec-
tions. Quinoline in methanol solutions (0.02, 0.05, 0.1, 0.2, 0.4, 15
1.0 mg/mL) were used as instrument check standards (R2 > 0.995
and intercept close to the origin). In all cases, the measured filter
10
tip lengths (M) are used to correct tip nicotine content and UV
absorbance/tip to the standard 10 mm tip length by multiplying
by the factor 10/M (St. Charles et al., 2009). Tip nicotine content 5
and UV absorbance/tip are proportional to the filter tip length
(Côté, unpublished data).
The complete procedure (smoking process, CFP and filter tip anal- 0
yses) was repeated on a separate occasion, to provide duplicate data 0 2 4 6 8 10 12 14 16
points for each calibration regime for each product in the study. Machine sm oked ISO tar yield (m g/cig)
For each cigarette product, filter tip and CFP tar or nicotine val-
Fig. 1. Estimated HS tar yields for each study year: , 2005 and , 2006. O, Means;
ues obtained with each calibration smoking regimes were used to
solid and dotted lines represent trendlines obtained from the average ISO and
construct calibration curves. The linear regression of nicotine yield Canadian intense tar yields measured for each product, respectively.
(mg/cig) against tip nicotine (mg/tip) was used to estimate HS nic-
otine yield (mg/cig) from the nicotine measured in the subject fil-
ter tips extract. Similarly, linear regressions of tar yield (mg/cig)
against UV absorbance/tip (UV abs/tip) provided calibration equa-
tions that were used to estimate HS tar yield (mg/cig) from UV
absorbance of the subject filter tips extract.

2.3. Statistical analysis

All statistical analyses were performed using Addinsoft XLSTAT

version 2008.6.02. The assumptions of normality and homogeneity
of variance of the residuals necessary for the validity of the ANOVA
model results were verified before interpreting the results. Data
were visualized by means of scatter plots (see Figs. 1 and 2). In or-
der to assess the relationship between the estimated HS tar and
nicotine yields and their measured ISO counterpart while account-
ing for the structure of the test, a three factor ANOVA including
second-order interactions was used to determine statistically sig-
nificant differences in HS yields across the range of products and
account for potential gender and study year effects. Where ANOVA
tests indicated a significant factor effect (p 6 0.05), a Tukey’s HSD
(Honestly Significant Difference) test was performed to compare
the different levels of the factors and identify which were statisti-
cally different in terms of estimated HS yields. Where ANOVA tests
indicated a significant interaction, it was usually more relevant to
compare only the levels of one factor within selected levels of the
Fig. 2. Estimated HS nicotine yields for each study year: , 2005 and , 2006. O,
other factor (as opposed to all possible factor level combinations).
Means; solid and dotted lines represent trendlines obtained from ISO and Canadian
For the significant interaction product  year, HS nicotine yields intense nicotine yields measured for each product, respectively.
obtained in 2005 for Product A were compared with those obtained
in 2006. The other combinations involving Product A were not
compared. In order to do so while correcting for multiple testing, An analysis of covariance (ANCOVA) model was applied to the
the following procedure was used: LSD (Least Significance Differ- data to study the effect of product format on estimated HS yields.
ence) tests were performed to identify which of the combinations The estimated HS tar or nicotine yields were the dependent vari-
of interest amongst all possible interactions were statistically dif- ables. The measured ISO tar and nicotine levels of each product
ferent in terms of estimated HS nicotine or tar yields. A Bonferroni and its squared value (to account for possible curvature in the rela-
correction was applied on the significance level of the comparisons tionships) were included as covariates and the product format, the
to maintain the experiment wise error rate at a = 0.05. For exam- gender and the year when the studies were performed were in-
ple, there were 10 combinations which compared the two study cluded as factors. All the second-order interactions were also in-
years for each of the 10 products. Thus, the significance level of cluded in the model. With the fitted model coefficients, the effect
5% was divided by 10 to obtain a = 0.005 which was the signifi- of the product format on the response variables were visualized
cance level used for the LSD test in that particular test. by means of regression curves (Figs. 3 and 4).
 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59 S55

18 data set because of missing demographic information. The recruit-

ment targets were well respected for all products. Table 4 summa-
16 rizes the demographics of the 1086 subjects. About the same
number of subjects was recruited for each product, each format
Estimated HS tar yield (mg/cig)

14 and each study year. Male smokers represented 55% of the total
subjects. Gender distribution varied depending on the product.
12 For some lower ISO yield products, more females were recruited,
while more males were recruited for some of the higher yield prod-
10 ucts. The recruited subjects were aged between 19 and 54 years
old. The exact age of each subject was not known as they were re-
8 cruited into groups with a five year age range (Table 4). The age
group distribution varied widely between products. Fig. 5 illus-
6 trates the relationship between the HS nicotine and tar yields
and the age group. No meaningful trend was observed. Therefore,
4 the age group effect was not tested in the ANOVA.
The average daily self-reported cigarette consumption (number
2 of cigarettes in the last 24 h) was obtained from the exit question-
naire. The mean daily cigarette consumption reported for the prod-
0 ucts ranged from 18.8 to 23.4 cig/day. The average daily cigarette
0 2 4 6 8 10 12 14 16 consumption of the subjects recruited in 2005 (22.1 cig/day) was
Machine sm oked ISO tar yield (m g/cig) significantly different (p = 0.003) from the daily consumption of
the 2006 subjects (20.6 cig/day) (results not shown).
Fig. 3. Product format effect on HS tar yields. Lines represent the predicted values
of the estimated HS tar yields for king (solid line) and regular (dotted line) size 3.2. Estimated HS tar and nicotine yields
products obtained by modeling the estimated HS yields against the measured ISO
tar values. Squares and lozenges represent means of estimated HS tar yields for king
and regular size products, respectively (with standard error bars). Full and open The linear regression data from calibration smoking (r2 between
symbols represent the 2005 and 2006 study years, respectively. 0.93 and 0.99) were used to estimate HS tar and nicotine yields
from the subjects’ filter tip measurements.
The estimated HS tar and nicotine yields obtained by each sub-
ject were plotted against the measured ISO tar or nicotine yields
2.0 for each product (Figs. 1 and 2). In Figs. 1 and 2 the lines corre-
spond to the ISO (solid line) and Canadian intense (dotted line) ma-
1.8 chine-smoked yields. The majority of the estimated HS tar (85%)
Estimated HS nicotine yield (mg/cig)

and nicotine (93%) yields were higher than the measured ISO
1.6
yields, but the average of these estimates for each product tended
1.4 to follow the same ranking order as the ISO and Canadian intense
machine-smoked yields. In contrast, the majority of the estimated
1.2 HS nicotine yields (98%) were lower than the Canadian intense nic-
otine yield and only one of the 1086 estimated HS tar yield results
1.0 was above the Canadian intense tar yield. For Product A, the differ-
ence between the lowest and highest individual estimated HS tar
0.8 and nicotine yields was 12.4 and 1.3 mg/cig for tar and nicotine,
respectively. For the other nine products, the differences in HS
0.6
tar and nicotine yields ranged between 19.2 and 24.5 mg tar/cig
0.4 and between 1.8 and 2.6 mg nicotine/cig.
The average estimated HS tar and nicotine yields obtained for
0.2 each product and each study year are presented in Table 5. The
year in which the studies were performed did not affect the esti-
0.0 mated HS tar yields as shown in the ANOVA table (Table 6). How-
0 0.2 0.4 0.6 0.8 1 1.2 1.4 ever, there was an effect of the interaction year  product on the HS
Machine smoked ISO nicotine yield (mg/cig) nicotine yield estimates (Table 7). The comparison of the two study
years for each of the 10 products showed that there was a signifi-
Fig. 4. Product format effect on HS nicotine yields. Lines represent the predicted cant difference (p = 0.001) between the estimated HS nicotine
values of the estimated HS nicotine yields for king (solid line) and regular (dotted yields obtained in 2005 and in 2006 for Product E only. The differ-
line) size products obtained by modeling the estimated HS yields against the
ence between the two years in terms of estimated HS nicotine
measured ISO nicotine values. Squares and lozenges represent means of estimated
HS nicotine yields for king and regular size products, respectively (with standard
yields for this product was 0.24 mg/cig (Table 5).
error bars). Full and open symbols represent the 2005 and 2006 study years, The statistical groupings of the products were performed by
respectively. product format (Table 8). Three distinct Tukey’s groups were ob-
tained for KS products’ estimated HS tar and nicotine yields: the
1 mg ISO tar yield product; the 4 and 7 ISO tar yield products;
3. Results and the 11 and 14 ISO tar yield products. The RS products were
separated in two groups for HS tar yields: the 4–8 mg ISO tar
3.1. Subject data yield products and the 12–14 mg ISO tar yields products. Three
RS groups were formed for HS nicotine yields: the 4 mg product,
A total number of 1105 subjects were recruited over the two the 5 and 7 mg ISO tar products and the 13 and 14 mg ISO tar
study years. Data from 19 subjects were excluded from the original products.
S56 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59

Table 4
Demographics of subjects from the 2005 and 2006 studies.

Format Product Number of Subjects (n = 1086)

Study Year Gender Age group
2005 2006 Male Female 19–24 25–29 30–34 35–39 40–44 45–49 50–54
(n = 566) (n = 520) (n = 489) (n = 597) (n = 190) (n = 133) (n = 190) (n = 146) (n = 148) (n = 147) (n = 132)
King sizea A (n = 107) 56 51 44 63 37 17 9 8 13 10 13
B (n = 110) 57 53 38 72 9 10 24 21 15 15 16
C (n = 108) 56 52 54 54 14 10 14 12 19 19 20
D (n = 114) 60 54 65 49 18 20 21 15 13 14 13
E (n = 104) 54 50 49 55 18 14 13 14 16 14 15
Regular sizeb F (n = 106) 55 51 56 50 12 9 25 16 13 24 7
G (n = 109) 57 52 58 51 21 16 20 12 15 16 9
H (n = 109) 56 53 75 34 21 18 28 16 9 12 5
I (n = 110) 58 52 74 36 27 10 17 16 19 13 8
J (n = 109) 57 52 83 26 13 9 19 16 16 10 26
a
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.

2.0 14

1.8 12
Estimated HS nicotine yield (mg/cig)

Estimated HS tar yield (mg/cig)

1.6
10

1.4
8
1.2
6
1.0

4
0.8

0.6 2

0.4 0
19-24 25-29 30-34 35-39 40-44 45-49 50-54
Age group

Fig. 5. Age group effect on HS nicotine and tar yields. Squares and lozenges represent means of estimated HS nicotine and tar yields, respectively (with 95% confidence
interval bars).

Table 5
Study year effect on HS nicotine and tar yields estimated using part filter analysis methodology.

Format Product Human-smoked nicotine yield (mg/cig) Mean (95% CI) Human-smoked tar yield (mg/cig) Mean (95% CI)
2005 2006 2005 2006
King sizea A 0.61 (0.06) 0.67 (0.08) 5.7 (0.6) 6.1 (0.7)
B 1.08 (0.08) 1.01 (0.12) 10.4 (0.8) 9.9 (1.2)
C 1.24 (0.11) 1.21 (0.13) 10.6 (0.9) 11.6 (1.2)
D 1.72 (0.11) 1.62 (0.13) 14.8 (1.0) 14.1 (1.2)
E 1.76c (0.11) 1.52c (0.13) 15.7 (1.0) 15.5 (1.3)
Regular sizeb F 0.95 (0.08) 1.02 (0.11) 9.6 (0.8) 10.4 (1.2)
G 1.30 (0.10) 1.09 (0.12) 11.7 (0.9) 10.4 (1.1)
H 1.27 (0.09) 1.20 (0.09) 11.3 (0.8) 10.7 (0.8)
I 1.54 (0.10) 1.56 (0.09) 13.1 (0.9) 14.5 (0.9)
J 1.60 (0.11) 1.77 (0.12) 14.9 (1.1) 15.0 (1.1)
a
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.
c
Significant difference (p = 0.001) between 2005 and 2006 estimated HS nicotine yields.

The gender of the subjects significantly affected the level of than females (p < 0.0001). The biggest gender difference was
estimated HS tar and nicotine yields (Tables 6 and 7). On average, for Product B, with 0.28 mg nicotine/cig and 2.9 mg tar/cig
HS yields obtained by male subjects were significantly higher (Table 9).
 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59 S57

Table 6
ANOVA table for HS tar yields estimates.

Source DF Sum of squares Mean squares Fisher’s F Pr > Fa

Year 1 0.160 0.160 0.012 0.914
Gender 1 443.177 443.177 32.040 <0.0001
Product 9 7408.788 823.199 59.515 <0.0001
Year * gender 1 6.747 6.747 0.488 0.485
Year * product 9 188.349 20.928 1.513 0.138
Gender * product 9 95.513 10.613 0.767 0.647
Error 1055 14592.614 13.832
Total 1085 23791.971
a
p Value for the Fisher’s F-test.

Table 7
ANOVA table for HS nicotine yields estimates.

Source DF Sum of squares Mean squares Fisher’s F Pr > Fa

Year 1 0.433 0.433 2.842 0.092
Gender 1 4.865 4.865 31.935 <0.0001
Product 9 101.482 11.276 74.013 <0.0001
Year * gender 1 0.173 0.173 1.136 0.287
Year * product 9 3.961 0.440 2.889 0.002
Gender * product 9 1.062 0.118 0.774 0.640
Error 1055 160.728 0.152
Total 1085 288.636
a
p Value for the Fisher’s F-test.

Table 8
Statistical comparison of estimated HS nicotine and tar yields from king size and
ready been demonstrated in several other studies (Gori and Lynch,
regular size products. 1983; Zacny and Stitzer, 1996; Benowitz et al., 2005; Hammond
et al., 2005). It has also been shown that, within the same subject,
Format Product HS nicotine LSD’s HS tar LSD’s
yield (mg/cig) groupingc yield groupingc
puffing behavior was highly stable over time (Scherer, 1999;
(mg/cig) Benowitz et al., 2005; Hammond et al., 2005). However, to our
knowledge, stability in average HS yields measured over time has
King sizea A 0.65 a 6.0 a
B 1.11 b 10.7 b not previously been demonstrated. We observed no significant dif-
C 1.24 b 11.2 b ferences in average HS tar yields before and after the introduction
D 1.65 c 14.2 c of the LIP regulations. For one product, there was a difference in HS
E 1.66 c 15.7 c
nicotine yields which cannot be explained. The major difference
Regular sizeb F 0.95 a 9.6 a between the cigarette products manufactured in 2005 and 2006
G 1.16 b 10.7 a
was the LIP cigarette paper introduced in 2006. For some products,
H 1.21 b 10.7 a
I 1.50 c 13.4 b tobacco density, filter ventilation and pressure drop had to be
J 1.60 c 14.0 b slightly modified to adjust for the presence of lower permeability
a
bands on the LIP paper. Only minor changes to the ISO tar and nic-
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.
otine yields were observed. Even with those modifications and the
c
Bonferroni correction a = 0.0025. fact that the subjects recruited in 2005 and 2006 were not the
same, the mean HS tar and nicotine yields associated with a spe-
cific product did not change significantly.
Figs. 3 and 4 illustrate the effect of cigarette format length on The estimated HS smoke yields reported in this study seem to
the estimated HS tar and nicotine yields. The means of the esti- be much lower than the human mimic yields obtained by Ham-
mated HS yields from KS products tend to plateau for the highest mond et al. (2006) with a sample of 51 smokers of Canadian ciga-
ISO tar yields. This plateau is not observed for RS products. Also, rette products. For 17 products having ISO tar yields ranging from 9
the means of the estimated HS tar yields obtained for most of to 15 mg/cig, they reported average human mimic yields of 24.7
the RS products were lower than for the KS products in the ISO and 2.0 mg/cig of tar and nicotine, respectively. This difference
tar yield range studied (4–15 mg/cig) (Fig. 3). All the observations could be explained by the methodology utilized to obtain the hu-
above also apply to the HS nicotine yield estimates (Fig. 4). man mimic yields: duplication of mean puff volume and mean
interval between puffs recorded from smokers for each product.
4. Discussion The duplication of smoking profiles could be a good method for
product comparison but is not recommended for the determina-
The part filter analysis methodology used in this study allowed tion of absolute yield values (Creighton and Lewis, 1978; Tobin
the estimation of the HS tar and nicotine yields from 10 commer- and Sackner, 1982). This method can lead to overestimation when
cial products smoked by Canadian smokers in their everyday envi- used to estimate smoke yields obtained by humans. First, it is gen-
ronment. These HS smoke yields data represent the maximum erally recognized that the puff volume and number are higher than
quantity of smoke available to the smoker rather than the absolute with natural smoking since smokers tend to deviate from their nor-
amount taken into the respiratory system. The wide ranges of HS mal smoking behavior when their puffing profiles are recorded
yields measured for each product are in agreement with the wide (Creighton and Lewis, 1978; Pickens et al., 1983; Hee et al.,
range of human smoking behavior and smoke intake that has al- 1995). The smokers need to be familiarized with smoking using a
S58 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59

Table 9
Gender effect on HS nicotine and tar yields estimated using part filter analysis methodology.

Format Product Human-smoked nicotine yield (mg/cig) mean (95% CI) Human-smoked tar yield (mg/cig) mean (95% CI)
Male Female Male Female
King sizea A 0.71 (0.09) 0.59 (0.06) 6.5 (0.8) 5.4 (0.5)
B 1.23 (0.11) 0.95 (0.08) 12.0 (1.1) 9.1 (0.8)
C 1.30 (0.12) 1.15 (0.11) 11.8 (1.0) 10.4 (1.1)
D 1.72 (0.11) 1.61 (0.14) 15.0 (1.0) 13.8 (1.2)
E 1.71 (0.14) 1.59 (0.12) 16.3 (1.3) 15.0 (1.1)
Regular sizeb F 1.01 (0.10) 0.95 (0.09) 10.2 (1.1) 9.7 (0.9)
G 1.25 (0.13) 1.15 (0.08) 11.6 (1.2) 10.5 (0.7)
H 1.26 (0.08) 1.19 (0.09) 11.2 (0.7) 10.6 (0.9)
I 1.63 (0.08) 1.39 (0.12) 14.3 (0.7) 12.7 (1.2)
J 1.72 (0.09) 1.57 (0.18) 15.3 (0.9) 13.9 (1.7)
a
Cigarette length: 84 mm.
b
Cigarette length: 72 mm.

cigarette holder. Second, the calibration of the flow meter is per-
formed with an unlit cigarette. The sensitivity of the flow meter
is slightly increased when the cigarette is lit, due to the change
in temperature (Guyatt and Baldry, 1988). Consequently, the total
volume of smoke produced by the smokers under these conditions
is usually overestimated. Finally, the puffing components are inter-
related and must be precisely recorded (Pickens et al., 1983). It is
therefore very important to exactly reproduce the volume of
smoke drawn, the interval between puffs and the shape of the puffs
for each smoker when attempting to estimate HS yields (Creighton
and Lewis, 1978). These reasons, combined with the more repre-
sentative population size of our study, suggest that the HS yields
reported in this study may be a better estimate of the average hu-
man smoking behavior of selected Canadian cigarettes. Moreover,
HS nicotine yields obtained using the part filter analysis were pre-
viously shown to correlate well with several biomarkers including
saliva cotinine (St. Charles et al., 2006; Shepperd et al., 2009) while
the human mimic nicotine yields were shown to weakly correlate
with salivary cotinine levels (Hammond et al., 2006).
The machine-smoked ISO tar and nicotine yields are generally
recognized as underestimating the yields obtained by smokers
(Benowitz, 2001; Hammond et al., 2007). Nicotine, cotinine and
CO exposure levels of commercial cigarette products can also be
related in an orderly manner to machine-smoked cigarette yields.
However, the reduction in machine-smoked cigarette yields fails
to accurately predict the reduction in exposure (Zacny and Stitzer,
1988). Our results are consistent with those findings. For the range
of tested products, the mean HS yields followed the same ranking
order as the ISO and Canadian intense machine-smoked yields.
However, the difference between the machine-smoked yields and
the HS yields obtained using the part filter analysis methodology
was smaller as the ISO yield increased.
Human smoking behavior is a dynamic process contrary to ma-
chine-smoking (Zacny and Stitzer, 1996). Our results clearly
showed that the Canadian intense smoking regime overestimates
the HS yields for the products assessed in this study for the vast
majority of smokers. The effect of the 100% vent blocking used in
the Canadian intense smoking regime is more important for highly
ventilated cigarettes. However, the complete blocking of ventila-
tion zone occurs in practice only in a minority of smokers and
when it happens, the smoker adjusts its smoking behavior by tak-
ing smaller and fewer puffs (Zacny and Stitzer, 1988; Porter and
Dunn, 1998; Baker and Lewis, 2001). The yield overestimation by
the Canadian intense smoking regime is even more important in
the case of Product A with a maximal HS tar yield value of about
12 mg/cig and about 20 mg/cig for the Canadian intense yield.
Benowitz et al. (1986, 2009) demonstrated that the exposure to
very low yield products (1 mg ISO tar) was considerably less than
for other products of higher ISO tar yields. The smaller range of
HS yields measured for Product A compared with that obtained
for the other products assessed in this study supports this finding.
The gender of the recruited smokers was shown to significantly
influence the level of estimated HS yields. Male smokers obtained
higher HS tar and nicotine yields. Gender differences in smoking
behavior can lead to higher yields from cigarettes smoked by males
(Hee et al., 1995; Melikian et al., 2007). Higher levels of nicotine,
cotinine, mutagens and thioethers were reported in male than in
female smokers (Hee et al., 1995). Based on those observations,
we can only stress the importance of using recruitment criteria
that fit the study objectives as they can impact significantly the
conclusions of such studies.
Different relationships between the estimated HS yields and the
ISO yields were observed for the two product formats tested (Figs.
3 and 4). Several differences in cigarette design can exist between
the KS and RS length products assessed. This study was not specif-
ically designed to determine which design parameter or combina-
tion of parameters had an impact on the smoking behavior.
Nevertheless, the difference between the two cigarette lengths is
in accordance with results obtained from an US survey where the
estimated HS yields of KS products were lower when compared
to 100 mm length products (St. Charles et al., 2010).
5. Conclusion
The introduction of banded papers in Canadian cigarettes com-
bined with other minor adjustments to the design to comply with
the LIP regulations did not affect the average HS yields associated
with a specific product. On the other hand, HS yield was influenced
by the cigarette format (length) and the gender of the recruited
smokers who participated to this study. In general, HS yields of
10 Canadian products led to observations supporting the conclu-
sions of several studies which used different methodologies to esti-
mate the exposure of smokers to cigarette smoke. Human smoking
behavior is not adequately represented by the ISO or the Canadian
intense smoking regimes but the same ranking order was obtained
for HS yields and ISO and Canadian intense yields.
Conflict of interest
This work was funded by Imperial Tobacco Canada Ltd. (ITCan).
France Côté and Richard Voisine are employees of ITCan. Cécile
Létourneau was employee of ITCan at time the studies were per-
formed and is now retired from ITCan. Gavin Mullard is employee
of British American Tobacco.
 F. Côté et al. / Regulatory Toxicology and Pharmacology 61 (2011) S51–S59
Acknowledgments
The authors thank Madeleine Ashley and Pam Saunders for
coordinating the logistics and the analytical work. We also thank
Dr. Derek Mariner for reviewing the draft paper.
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